Extrauterine Adenomyoma of the Lung: A Rare Case Report

On October 31, 2023, a 34-year-old woman was referred to our department for evaluation of pulmonary nodular shadows. The pulmonary findings were detected incidentally on preoperative chest computed tomography performed before laparoscopic bilateral salpingectomy for ectopic pregnancy. Her past surgical history comprised an abdominal myomectomy for uterine fibroids in 2013, laparoscopic myomectomies in 2017 and 2019, and an uncomplicated cesarean section in 2021. She has one child. She denied smoking, a family history of malignancy, cough, sputum production, chest pain, hemoptysis, dyspnea, or menstrual-cycle-related respiratory symptoms. Initial laboratory testing on October 11, 2023, showed a CA125 concentration of 72.17 U/mL (upper limit of normal [ULN], 30.2 U/mL). Routine blood counts, C-reactive protein, hepatic and renal function tests, myocardial enzymes, and electrocardiography results were all within normal limits. A serum β-hCG level of 81.8 mIU/mL (ULN, 10 mIU/mL) was recorded on October 28, 2023. CT scan, pelvic MRI, and transvaginal ultrasonography were subsequently performed. Pre-operative chest CT (October 17, 2023; Figure 1A and B ) demonstrated multiple pulmonary masses and nodules, raising suspicion of metastatic disease. Pelvic MRI (October 20, 2023; Figure 1C and D ) revealed a cystic lesion in the right adnexa with abnormal enhancement (21×38 mm and 15×28 mm), uterine adenomyosis with multiple fibroids, and an abnormal signal in the right uterine wall (14×21 mm). Pelvic encapsulated fluid and a uterine scar diverticulum were also present. Ultrasonography of the uterus and adnexa (October 21, 2023) identified a heterogeneous mass adjacent to the right ovary, adenomyosis with concomitant uterine fibroids, and a cystic lesion containing encapsulated fluid near the left ovary. Figure 1 Chest CT, pelvic MRI, and histopathological and immunohistochemical findings. ( A ) Chest computed tomography (CT) image at the level of the bilateral upper lobes and superior segments of the bilateral lower lobes showing multiple pulmonary nodules and masses in both lungs, raising suspicion for metastatic disease. ( B ) Chest CT image at the level of the right middle lobe, lingular segment of the left upper lobe, and basal segments of the bilateral lower lobes showing additional bilateral pulmonary nodules and masses, also suggestive of metastatic lesions. ( C ) Pelvic T2-weighted magnetic resonance imaging (MRI) image at the level of the uterine body showing an enlarged uterine corpus, measuring approximately 65 mm × 65 mm, with multiple small nodular abnormal signals in the myometrium. An abnormal signal measuring approximately 14 mm × 21 mm is also visible in the right uterine wall. These findings were consistent with adenomyosis with multiple uterine fibroids.( D ) Pelvic T2-weighted MRI image at the level of the femoral heads showing a low-signal nodular lesion in the right adnexal region, measuring approximately 26 mm × 19 mm, and multiple high-signal lesions in the left adnexal region, the largest measuring approximately 67 mm × 30 mm. Additional right adnexal cystic lesions, measuring approximately 21 mm × 38 mm and 15 mm × 28 mm, were identified on MRI and showed abnormal enhancement on contrast-enhanced sequences. Together with the elevated serum β-hCG level, these findings were considered compatible with ectopic pregnancy. Pelvic encapsulated fluid and a uterine scar diverticulum were also noted. ( E ) Histopathological image at low magnification (×40) showing tumor-like smooth muscle tissue with a small number of glandular structures. ( F ) Histopathological image at higher magnification (×100) showing smooth muscle bundles and scattered glandular elements. Immunohistochemistry showed positivity for estrogen receptor, progesterone receptor, desmin, and h-caldesmon, few CD10-positive cells, negativity for S-100 and HMB45, and a Ki-67 index of approximately 2%, supporting the diagnosis of pulmonary benign uterine adenomyoma. Composite: 2 chest CT, 2 pelvic MRI, 2 histology micrographs on light background. Chest CT, pelvic MRI, and histopathological and immunohistochemical findings. ( A ) Chest computed tomography (CT) image at the level of the bilateral upper lobes and superior segments of the bilateral lower lobes showing multiple pulmonary nodules and masses in both lungs, raising suspicion for metastatic disease. ( B ) Chest CT image at the level of the right middle lobe, lingular segment of the left upper lobe, and basal segments of the bilateral lower lobes showing additional bilateral pulmonary nodules and masses, also suggestive of metastatic lesions. ( C ) Pelvic T2-weighted magnetic resonance imaging (MRI) image at the level of the uterine body showing an enlarged uterine corpus, measuring approximately 65 mm × 65 mm, with multiple small nodular abnormal signals in the myometrium. An abnormal signal measuring approximately 14 mm × 21 mm is also visible in the right uterine wall. These findings were consistent with adenomyosis with multiple uterine fibroids.( D ) Pelvic T2-weighted MRI image at the level of the femoral heads showing a low-signal nodular lesion in the right adnexal region, measuring approximately 26 mm × 19 mm, and multiple high-signal lesions in the left adnexal region, the largest measuring approximately 67 mm × 30 mm. Additional right adnexal cystic lesions, measuring approximately 21 mm × 38 mm and 15 mm × 28 mm, were identified on MRI and showed abnormal enhancement on contrast-enhanced sequences. Together with the elevated serum β-hCG level, these findings were considered compatible with ectopic pregnancy. Pelvic encapsulated fluid and a uterine scar diverticulum were also noted. ( E ) Histopathological image at low magnification (×40) showing tumor-like smooth muscle tissue with a small number of glandular structures. ( F ) Histopathological image at higher magnification (×100) showing smooth muscle bundles and scattered glandular elements. Immunohistochemistry showed positivity for estrogen receptor, progesterone receptor, desmin, and h-caldesmon, few CD10-positive cells, negativity for S-100 and HMB45, and a Ki-67 index of approximately 2%, supporting the diagnosis of pulmonary benign uterine adenomyoma. Collectively, these findings indicated the presence of pulmonary nodular lesions, a cystic lesion in the right adnexa, uterine adenomyosis with fibroids, and a uterine scar diverticulum. An initial working diagnosis of pulmonary shadow consistent with metastasis, post-surgical state after right cornual ectopic pregnancy and salpingectomy, uterine fibroids, and uterine adenomyosis was therefore established. Subsequently, on November 3, 2023, the patient underwent a CT-guided lung biopsy. Histopathology of the right upper lobe lesion revealed smooth muscle tissue with scattered endometrial glandular structures, consistent with adenomyoma; definite endometrial stroma was not identified in the limited biopsy specimen. Immunohistochemistry results were as follows: estrogen receptor (+) and progesterone receptor (+) were positive; desmin (+) and h-caldesmon (+) were positive; CD10 showed few positive cells; S-100 and HMB45 were negative; and Ki-67 was approximately 2% ( Figure 1E and F ). A final diagnosis of pulmonary benign uterine adenomyoma was established. On November 15, 2023, the patient commenced treatment with a subcutaneous injection of goserelin acetate (3.6 mg), a synthetic gonadotropin-releasing hormone (GnRH) agonist, administered every 28 days as part of her endocrine therapy. On May 8, 2024, letrozole (2.5 mg, administered orally once daily), an aromatase inhibitor, was added to further suppress estrogen production because the lesion was considered hormone-responsive. Follow-up chest CT on February 8, 2024 demonstrated multiple bilateral pulmonary lesions without obvious interval change compared with prior CT. A repeat chest CT on November 22, 2024, performed after the addition of letrozole, again showed stable pulmonary lesions without progression ( Figure 2 ). Throughout follow-up, the patient remained free of cough, sputum production, chest pain, hemoptysis, and dyspnea, and no treatment-related adverse effects were observed. Figure 2 Radiological evolution of pulmonary lesions during endocrine therapy. Serial chest CT images showing the radiological course of the pulmonary lesions before and during endocrine therapy. ( A ) Pretreatment chest CT obtained on November 1, 2023 showed multiple bilateral pulmonary nodular lesions and masses. ( B ) Follow-up chest CT obtained on February 8, 2024, after initiation of goserelin acetate therapy, showed no obvious interval progression. ( C ) Follow-up chest CT obtained on November 22, 2024, after the addition of letrozole, again demonstrated stable bilateral pulmonary lesions without obvious progression. These findings indicate radiological stability during endocrine therapy. Radiology figure: 3 images (A, B, C) with 2 axial chest CT lung slices showing round opacities on black background. Radiological evolution of pulmonary lesions during endocrine therapy. Serial chest CT images showing the radiological course of the pulmonary lesions before and during endocrine therapy. ( A ) Pretreatment chest CT obtained on November 1, 2023 showed multiple bilateral pulmonary nodular lesions and masses. ( B ) Follow-up chest CT obtained on February 8, 2024, after initiation of goserelin acetate therapy, showed no obvious interval progression. ( C ) Follow-up chest CT obtained on November 22, 2024, after the addition of letrozole, again demonstrated stable bilateral pulmonary lesions without obvious progression. These findings indicate radiological stability during endocrine therapy.

Adenomyosis is a benign gynecological condition characterized by the presence of endometrial glands and stroma within the myometrium. 1 Although its true prevalence remains uncertain, a recent meta-analysis reported a pooled prevalence of isolated adenomyosis in women with subfertility of 10% (95% confidence interval [CI], 6–15%), with pronounced geographical variation: Australia had the highest prevalence at 19% (95% CI 12–27%), whereas Asia had a lower prevalence of 5% (95% CI 1–12%). 2 Clinically, adenomyosis most commonly affects women of reproductive age and presents with dysmenorrhea, prolonged menstrual bleeding, menorrhagia, and uterine enlargement. 3 Histopathology remains the diagnostic gold standard; however, transvaginal ultrasonography is now the preferred first-line modality. 4 When both direct ultrasonographic features (eg, myometrial cysts, hyperechogenic islands) and indirect features (eg, asymmetrical myometrial thickening, globular uterus) were considered, the pooled prevalence of isolated adenomyosis was 11% (95% CI 7–16%). Limiting the analysis to indirect features alone reduced the prevalence to 0.45% (95% CI 0–1%). 2 Adenomyosis can manifest in two distinct patterns: diffuse or focal. It is classified as diffuse when it involves the junctional zone and outer myometrium, while it is considered focal when it presents as a localized nodular adenomyotic lesion. 5 , 6 When adenomyomas are located outside the uterus, they are referred to as extrauterine adenomyomas (EAs). 7 EAs are characterized as well-defined, tumor-like masses composed of smooth muscle tissue, endometrioid glands, and endometrial stroma. They share similarities with their uterine counterparts in most aspects. 8 EA is a rare condition, typically found in the pararectal space, ovary, peritoneum, or broad ligament. 9 Other reported sites of involvement include the lung, with isolated cases of EAs found in the pulmonary region. 10 To further our understanding of this rare pathological phenomenon, we present a case of pulmonary benign extra-uterine adenomyoma, confirmed by histopathological analysis. By summarizing and analyzing this case, we aim to not only refine the diagnostic approach for such conditions but also to accumulate valuable clinical insights that may serve as a reference for future diagnostic and therapeutic practices.

The first case of EA was reported by Cozzutto et al in 1981. 11 A subsequent review documented 34 cases at pelvic and extrapelvic sites: 19 confined to the pelvis, 8 extrapelvic, and 7 involving multiple locations. 7 The present report, therefore, describes a rare case of benign uterine adenomyoma presenting as a pulmonary lesion. The woman, who had undergone several gynecological operations, including myomectomy and cesarean section, presented with pulmonary nodules that raised suspicion of a tumor. This case highlights the considerable diagnostic challenge posed by pulmonary benign uterine adenomyoma, particularly in young women with multiple pulmonary lesions, as its radiological appearance may closely resemble that of primary or metastatic tumors. Conventional imaging modalities, including CT and MRI, lack sufficient specificity to reliably differentiate these benign lesions from malignant disease. In addition, many patients remain asymptomatic, and lesions are frequently identified incidentally during routine imaging examinations, potentially contributing to delayed diagnosis or misdiagnosis. Definitive diagnosis therefore depends on histopathological and immunohistochemical evaluation. Notably, serial chest CT examinations through November 2024 showed no progression during endocrine therapy, suggesting that hormonal suppression may represent a reasonable therapeutic option for selected patients. Overall, this case highlights the need to include benign adenomyoma in the differential diagnosis of pulmonary masses, particularly in individuals with documented uterine adenomyosis. Five proposed theories may elucidate the pathogenesis of benign adenomyomas in the lung. The first theory, Defective Müllerian Duct Fusion, posits that abnormalities in the fusion of the Müllerian ducts can lead to developmental anomalies such as a unicornuate uterus with a rudimentary horn, which may later detach and implant elsewhere, thereby giving rise to adenomyomas. 12 This theory is closely associated with congenital urogenital malformations. The second theory, Müllerianosis, suggests that remnants of Müllerian cells may become incorporated into various organs during development, subsequently forming adenomyomas. 13 However, this theory does not apply to cases with a history of endometriosis or prior surgical interventions. The third theory, Smooth Muscle Cell Metaplasia, suggests that endometriotic lesions may undergo metaplastic transformation into smooth muscle cells, thereby contributing to the formation of adenomyomas. 11 However, this hypothesis fails to account for the histopathological findings observed in the case under study. The fourth theory, Mesenchymal Metaplasia, proposes that mesenchymal cells have the potential to differentiate into endometrial tissue or smooth muscle under hormonal influence. 14 Histopathological findings in cases supporting this theory often reveal predominant smooth muscle with focal areas of endometrial tissue. A similar histopathological pattern was observed in our case, with the presence of both smooth muscle tissue and glandular structures aligning with the characteristics of mesenchymal metaplasia. This supports the application of this theory to explain the formation of the adenomyoma in our patient. In addition, the fifth theory highlights a potential procedural risk: Surgical Uterine Tumor Resection. Recent studies suggest that during laparoscopic electrosurgical resection of uterine tumors, some residual tissue may be inadvertently dispersed into the abdominal cavity. This spread could increase the risk of extrauterine metastasis. 15 Long-term follow-up of EA has shown favorable outcomes, and pulmonary benign extra-uterine adenomyoma is recognized as a benign tumor. Management encompasses pharmacological and surgical options. Surgical excision remains the first-line treatment for EA, 7 and resection of metastatic deposits is typically associated with a favorable prognosis. Nevertheless, several authors recommend monthly GnRH agonists after surgery to suppress the estrogen-driven proliferation of neoplastic tissue and to prevent recurrence. 16 Therapy for metastatic adenomyoma follows principles analogous to those for uterine adenomyoma, with the primary aim of reducing endogenous estrogen and progesterone production or activity and inhibiting adenomyoma differentiation. GnRH antagonists have also demonstrated benefit in treating adenomyoma. 17 A case series involving five patients with EA reported that GnRH agonists and aromatase inhibitors were advantageous in inoperable cases or when patients wished to avoid surgical risk. 18 Another report involving two patients showed durable benefit (4–10 y) from GnRH agonist therapy after surgical resection. 16 However, the long-term efficacy of endocrine therapy remains uncertain because of the limited number of reported cases and the lack of extended follow-up data. In the present case, medical therapy was administered without complications or adverse effects, further supporting pharmacological management as a means of preventing recurrence after surgery. This report describes an exceptionally rare pulmonary benign extra-uterine adenomyoma, yet several limitations should be noted. First, because it concerns a single case, a direct comparison between pharmacological and surgical approaches was not possible, which limits the determination of the optimal treatment modality for similar patients. Second, although follow-up chest CT through November 2024 showed stable pulmonary lesions, the follow-up interval remains relatively short; more extended observation is needed to assess the risk of recurrence or new metastases. Finally, although histopathology confirmed the diagnosis, further studies are needed to elucidate the molecular mechanisms underlying the metastatic behavior of adenomyoma.

In this report, we describe a pulmonary benign extra-uterine adenomyoma—a distinctly rare clinical entity. Diagnosis is challenging and requires histopathological confirmation. This case underlines the need to include pulmonary benign metastasizing adenomyoma in the differential diagnosis of pulmonary masses, particularly in patients with a prior history of uterine adenomyosis. Although surgical excision is usually first-line therapy for EAs, pharmacological options such as GnRH agonists offer an effective alternative for patients who are inoperable or who wish to avoid surgery. Larger case series and extended follow-ups are essential for establishing comprehensive management guidelines and improving clinical outcomes. Further research should also elucidate the molecular mechanisms that govern the behavior of benign adenomyoma and optimize therapeutic strategies for this uncommon condition.